Dissertation
IMMUNITY AND PATHOGENESIS OF THEILERIA EQUI AND EQUINE HEPACIVIRUS INFECTION IN IMMUNOCOMPETENT AND IMMUNODEFICIENT HORSES
Doctor of Philosophy (PhD), Washington State University
01/2013
Handle:
https://hdl.handle.net/2376/118121
Abstract
Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, the phenotype of schizont infected cells was determined in vitro by IFA and flow cytometry, and subsequently demonstrated in vivo by infecting foals with severe combined immunodeficiency (SCID). These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis, breed susceptibility, and strain virulence.
Equine hepacivirus (EHCV) (also called non-primate hepatitis virus) is the closest genetic relative of HCV identified to date. Since the pathogenesis of EHCV has not been defined, its relevance as a disease model for HCV is unknown. In this study, EHCV pathogenesis was examined by infecting four adult horses, two juvenile horses (foals) and two foals with severe combined immunodeficiency (SCID). Plasma viremia and liver tropism were assessed by qRT-PCR and in situ hybridization, respectively. Liver disease was determined with serum biochemical analysis and liver biopsy. Viremia ranging from 104-107 copies/ml was detectable 1 week post-infection (WPI) and persisted in 6 of 8 horses. Adult horses had biochemical evidence of acute liver disease 4-8 WPI, random hepatocellular necrosis in liver biopsies, and intrahepatocyte EHCV RNA detected with in situ hybridization. SCID foals and immunocompetent foals had minimal evidence hepatitis despite having similar levels of viremia and intrahepatic viral RNA. These findings suggest that acute EHCV-related disease is mediated by the adaptive immune system and possibly dependent other factors that vary with host age. Together these data are the first to document EHCV infection kinetics, hepatotropism, and associated liver pathology, and demonstrate that EHCV is a tenable model for HCV.
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Details
- Title
- IMMUNITY AND PATHOGENESIS OF THEILERIA EQUI AND EQUINE HEPACIVIRUS INFECTION IN IMMUNOCOMPETENT AND IMMUNODEFICIENT HORSES
- Creators
- Joshua David Ramsay
- Contributors
- Robert H Mealey (Advisor)Robert H Mealey (Committee Member)Wendy C Brown (Committee Member)Steven A Hines (Committee Member)Donald P Knowles (Committee Member)Glen A Scoles (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 61
- Identifiers
- 99900581847501842
- Language
- English
- Resource Type
- Dissertation